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Biomedical subjects

M A Preece

Publications and source records attributed to M A Preece.

At least 109 records · Page 6Linked to original sources

Growth in atopic eczema: a controlled study by questionnaire.

The parents of 128 children with atopic eczema and 117 healthy control children responded to a questionnaire that included measurement of their own and their children's heights at home after standardised instructions. When cases and controls were compared there was no significant difference in parental height but the children with eczema were significantly shorter than the healthy control group. This difference remained significant when children with associated asthma were excluded from the analysis.

Adolescent

Growth hormone secretion in Turner's syndrome and influence of oxandrolone and ethinyl oestradiol.

We investigated 24 hour growth hormone secretion by intermittent 20 minute blood sampling in 34 prepubertal patients with Turner's syndrome, aged 4.3-12.4 years. Growth hormone profiles were analysed by the PULSAR programme and results expressed as the sum of growth hormone pulse amplitudes. Six patients had abnormal growth hormone pulse frequencies. In the remaining 28, growth hormone pulse amplitudes declined significantly with increasing age, but there was no correlation between growth hormone pulse amplitudes and growth rates. Concentrations of insulin like growth factor-1 (IGF-1) rose with age but did not correlate with either growth rates or growth hormone secretion. Fifteen patients were given oxandrolone and 11 low dose ethinyl oestradiol. Both agents increased height velocity without increasing growth hormone secretion. We conclude that the relation between growth hormone secretion and growth in Turner's syndrome is less certain than in normal children. End organ resistance is probably due to a skeletal dysplasia. Both oxandrolone and low dose ethinyl oestradiol improve the growth of girls with Turner's syndrome, but their mechanism of action remains uncertain.

Body Height

Relationship between insulin, insulin-like growth factor I, and dehydroepiandrosterone sulfate concentrations during childhood, puberty, and adult life.

The relationships between plasma insulin, insulin-like growth factor I (IGF-I) and dehydroepiandrosterone sulfate (DHEAS) concentrations in normal subjects have not been defined. We performed iv glucose tolerance tests on 102 normal subjects, aged 5-20 yr. The subjects were divided into 4 groups according to pubertal stage (Tanner): A, stage 1 (n = 22); B, stages 2 and 3 (n = 17); C, stages 4 and 5 (n = 20); and D, adult, greater than 17 yr (n = 43). The basal plasma IGF-I and insulin concentrations and incremental 0-60 min insulin areas in response to glucose rose significantly throughout puberty (P less than 0.001 for all parameters) and declined to prepubertal levels by the third decade of life. There was a strong positive correlation between log fasting plasma insulin vs. log plasma IGF-I (r = 0.625; P less than 0.001) and log incremental 0-60 min insulin areas vs. log plasma IGF-I (r = 0.572; P less than 0.001). Plasma DHEAS concentrations were measured in groups A-C (n = 59); these also rose throughout puberty. There was strong correlations between log plasma DHEAS and log basal or stimulated (incremental 0-60 min areas) insulin responses (P less than 0.001). To assess the relationship between plasma DHEAS and insulin before puberty, we analyzed the data from group A separately. Plasma DHEAS concentrations tended to be higher in children 9 yr of age or older than in those less than 9 yr old, whereas basal and stimulated plasma insulin levels were similar. We found no correlation between log plasma insulin (fasting or stimulated responses) and log plasma DHEAS concentrations in group A (P greater than 0.05). In conclusion, we found a strong relationship between plasma insulin and IGF-I throughout childhood and puberty and during adult life. This finding suggests that insulin may be important for normal growth during childhood. There was no correlation between plasma insulin and DHEAS concentrations in prepubertal children, which suggests that adrenarche does not influence insulin levels.

Adolescent

Pulsatile gonadotropin secretion in pubertal children with chronic renal failure.

We have examined physiological nocturnal secretion of gonadotropins in 6 boys and 2 girls with end-stage renal disease, who had either delayed or disturbed puberty. The 5 patients treated by dialysis had reduced gonadotropin pulsatility for their stage of pubertal maturation, whereas the 3 patients with successful kidney grafts demonstrated a higher nocturnal rise and increased amplitude of gonadotropin pulsatility. It is suggested that the improved gonadotropin pulsatility of transplanted patients is due to their restored renal function.

Adolescent

A monoclonal antibody to human insulin-like growth factor-I: characterization, use in radioimmunoassay and effect on the biological activities of the growth factor.

A monoclonal antibody (BPL-M23) to insulin-like growth factor-I (IGF-I) was obtained following immunization of BALB/c mice with human IGF-I conjugated to ovalbumin. The affinity constant of BPL-M23 for IGF-I was 10.5 litres/nmol and the cross-reactivities of IGF-II, multiplication-stimulating activity III-2 and insulin were 0.8, 0.03 and less than 0.0001% respectively. Porcine, bovine, ovine and rabbit sera, but not rat or mouse sera, showed substantial reactivity with the antibody. Comparison of radioimmunoassay analyses of 54 human serum samples from normal subjects and acromegalic and GH-deficient patients using BPL-M23 and a polyclonal rabbit antiserum (R557A) to human IGF-I showed a high correlation, indicating the usefulness of the monoclonal antibody in radioimmunoassay. Monoclonal antibody BPL-M23 was capable of abolishing the sulphation, mitogenic and insulin-like activities of IGF-I in in-vitro bioassays, suggesting that these activities may rely upon the same receptor-binding site which is near to the antibody-binding site.

Animals

Insulin like growth factor-I, protein kinase-C, calcium and cyclic AMP: partners in the regulation of chondrocyte mitogenesis and metabolism.

The possible role of protein kinase-C (PKC), calcium and cyclic AMP (cAMP) in mediating the metabolic and mitogenic effects of insulin-like growth factor-I (IGF-I) on chondrocytes was investigated using a PKC activator (phorbol ester 12,13-dibutyrate, PDBU), a PKC inhibitor (compound H7), a calcium channel blocker, (verapamil) and a cAMP analogue (dibutyryl cAMP). IGF-I and PDBU stimulated sulphate and thymidine incorporation by chondrocytes. Both of these effects were inhibited by compound H7. Verapamil inhibited IGF-I- and PDBU-stimulated sulphate incorporation, but contrastingly stimulated basal and enhanced IGF-I and PDBU stimulation of thymidine incorporation. Dibutyryl cAMP increased basal and IGF-I-stimulated sulphate incorporation but inhibited but inhibited both basal and IGF-I stimulation of thymidine incorporation. These results suggest a harmonic overlap between the activities of PKC and cAMP-dependent PKA enzyme systems, and calcium balance in the mitogenic and metabolic process of the chondrocyte.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Gonadotrophin, growth hormone and prolactin secretion in children with primary hypothyroidism.

We have studied eight children with primary hypothyroidism (6F, 2M) aged 6.7 to 14.2 years. The girls were prepubertal and the boys had early normal pubertal development. Overnight secretion of LH, FSH, TSH, PRL and GH, and ovarian ultrasound morphology were assessed before and up to 9 months after commencing thyroxine treatment. Serum FSH concentrations in all the girls were increased above LH levels and severe hypothyroidism was associated with reduced GH secretion. These abnormalities reversed with thyroxine treatment. The boys had less severe hypothyroidism and did not demonstrate abnormal gonadotropin or GH secretion. We conclude that primary hypothyroidism in childhood is associated with widespread disturbance of pituitary function, including increased FSH secretion often without signs of early sexual maturation.

Adolescent

Physiological growth hormone (GH) secretion during the recovery from psychosocial dwarfism: a case report.

We describe a 6.4 year old boy who had reversible GH insufficiency secondary to psychosocial dwarfism. On removal to a more favourable environment we observed the recovery of physiological GH secretion by progressive increase in GH pulse amplitude. These observations are relevant to our understanding of the control of GH secretion in that GH pulse frequency appears invariable and alteration in GH secretion is by pulse amplitude modulation.

Child

Adolescent growth and pubertal progression in the Silver-Russell syndrome.

The pattern of growth and development of 18 adolescent children with the Silver-Russell syndrome was studied. Mature height was about -3.6 standard deviation scores in both sexes. This is comparable to the height reduction at diagnosis, which has been reported previously. The pattern of puberty and adolescent growth was essentially normal and occurred at a marginally earlier time than normal, although in this small series the differences were not significant. In the girls there was a tendency to gain subcutaneous fat after puberty. This trend was not apparent in the boys.

Adolescent

Double blind placebo controlled trial of low dose oxandrolone in the treatment of boys with constitutional delay of growth and puberty.

Nineteen boys, mean age 14.4 years (range 12.9-16.3), with constitutional delay of growth and puberty were randomised into two groups in a double blind fashion for a three month period. Ten boys received oxandrolone, 2.5 mg per day (mean dose 0.072 mg/kg/day), and nine boys were treated with placebo. Mean growth velocity increased from 4.5 cm/year in the oxandrolone treated group to 9.6 cm/year in three months, and this was sustained at 8.6 cm/year after cessation of treatment. In the placebo treated group, growth rate showed no alteration from 5.1 cm/year to 5.2 cm/year; boys in this group were then treated with oxandrolone, 2.5 mg a day (mean dose 0.073 mg/kg/day) for three months and growth velocity accelerated to 8.6 cm/year. Serum concentrations of insulin-like growth factor -1/somatomedin-C (IGF-1) increased during oxandrolone treatment and continued to rise after treatment had ceased. There was no change in serum IGF-1 concentration during treatment with placebo. Oxandrolone, when used in an appropriate regimen, is an effective, safe treatment for boys with constitutional delay of growth and puberty.

Adolescent

Precocious or early puberty and growth failure in girls treated for acute lymphoblastic leukaemia.

We have studied 41 children with early or precocious puberty who have been treated for acute lymphoblastic leukaemia with prophylactic cranial irradiation (1,800-2,400 cGy) accompanied by intrathecal methotrexate and systemic chemotherapy. Mean age at radiotherapy was 3.9 years (range 1.7-7.7) in the girls and 4.8 years (range 2.6-7.8) in the boys. Mean age at the onset of puberty was 8.6 years (range 6.7-9.7) in the girls and 9.3 years (range 7.8-10.3) in the boys. Of the 41 children with early puberty (greater than 1.4 SD from the mean) 36 were females and 5 were males. 21 of the 36 girls had an absent or inadequate growth acceleration of puberty. 7 of 12 girls who had a pharmacological test of growth hormone (GH) secretion had GH insufficiency (peak level less than 20 mU/l). Early or precocious puberty combined with GH insufficiency may produce severe growth failure and we have used a treatment regimen of a gonadotrophin-releasing hormone analogue, in order to reduce the rate of epiphyseal maturation, combined with biosynthetic GH to increase or sustain growth rate. We have treated 4 girls in this manner. During a mean treatment period of 0.86 years, height SDS for bone age rose from a mean of -1.06 to -0.59. Longer treatment periods will be required to assess the effect on final height.

Child

Physiological growth hormone secretion in children with short stature and intra-uterine growth retardation.

31 prepubertal children with short stature [mean height standard deviation score (SDS) -2.84] and low birth weight (mean -2.82 SDS) were studied. Mean age was 6.0 years and mean height velocity SDS was -0.76. Patients were classified as having either the clinical characteristics of Russell-Silver syndrome (RSS) (4 F, 13 M) or not (4 F, 10 M). All children had an overnight profile of spontaneous growth hormone (GH) secretion. 4 children achieved a maximum GH concentration of less than 20 mU/l. 9 children with RSS secreted only one large GH peak during the night. Most of the non-RSS group had normal GH pulse frequency but 3 boys had a fast-frequency pattern. Abnormal GH secretion may contribute towards growth failure in children with low birth weight/RSS.

Body Height

New concepts of the growth spurt of puberty.

The timing of the growth spurt of normal children does not affect their final height attainment. Growth rate during the growth acceleration of puberty correlates with changes in GH, and not sex steroid, secretion. GH secretion during puberty is pulse amplitude, and not frequency, modulated. In both central precocious puberty and normal puberty suppressed with a GnRH analogue, the rate of epiphyseal maturation is decreased as are GH pulse amplitude and growth, but with no influence on final height.

Adolescent

Prediction of adult height: methods and problems.

The three commonly used methods of height prediction employ various combinations of anthropometric data and bone age. In normal children, the regression type methods are preferable, though they do not perform well in the more severe disorders of growth. They are extremely dependent upon the limitations of the method of bone age determination that is used. A major source of error is the inability to predict the timing or the intensity of the adolescent growth spurt. Until this proves possible it is unlikely that significant improvements can be made.

Adolescent